1. Field of the Invention
The present invention relates to a process for the recovery and purification of organic acids from an aqueous solution, such as a fermentation broth
2. Related Art
Organic acids are important chemicals of commerce, having many uses in the food and pharmaceutical industries. Lactic acid, for example, can be added to a variety of foodstuffs as a preservative and is used in medical preparations and as a monomer in the manufacture of biodegradeable plastics used in sutures, prosthetics and controlled release drug delivery systems.
Organic acids can be produced either by chemical synthesis or by microbial fermentation. Historically, organic acids were produced for animal fat or vegetable oil sources or from petroleum sources in substantially non-aqueous systems. However, since a number of microorganisms are known to produce valuable organic acids, methods have been developed for the recovery of organic acids produced by microbial fermentation. See e.g., U.S. Pat. Nos. 5,681,728; 5,034,105; 5,002,881; and 4,882,277.
In the process for preparing organic acids, the step of fermentation is relatively simple. However, the steps of recovery and purification of the product, i.e. an organic acid, are usually complicated with poor efficiency. For example, recovery of a representative organic acid, 2-keto-L-gulonic acid, is made as follows.
2-keto-L-gulonic acid is a significant intermediate in the preparation of D-ascorbic acid (vitamin C), an essential nutrient. In the past, 2-keto-L-gulonic acid has been synthesized on an industrial scale using the Reichstein method (Helvetica Chimica Acta 17:311 (1934)). This method however, has a number of disadvantages for commercial application, including the use of large quantities of solvents and the involvement of a number of complex reaction steps.
According, as an alternative to the Reichstein method, a number of processes employing one or more microorganisms have been developed for the commercial production of 2-keto-L-gulonic acid by fermentation. U.S. Pat. No. 2,421,611, for example, discloses a method involving microbial oxidation of D-glucose to 5-keto-L-gluconic acid, followed by chemical or microbial reduction to D-idonic acid and subsequent microbial oxidation to 2-keto-L-gulonic acid. Fermentative pathways involving oxidation of D-sorbose to 2-keto-L-gulonic acid via a sorbosone intermediate have also been developed using, for example, Gluconobacter oxydans (U.S. Pat. Nos. 4,935,359; 4,960,695; and 5,312,741). Pseudogluconobacter saccharoketogenes (U.S. Pat. No. 4,877,735). Pseudomonas sorbosoxidans (U.S. Pat. Nos. 4,892,823 and 4,933,289), and mixtures of microorganisms (U.S. Pat. Nos. 3,234,105, 3,907,639; and 3,912,592).
Similar to fermentation processes utilized for the manufacturer of other organic acids, the 2-keto-L-gulonic acid which results as a metabolic product is usually neutralized by the addition of a base, e.g. sodium hydroxide or calcium hydroxide, in order to control the pH value and maintain favorable fermentation conditions. The product of the fermentation is an aqueous, biomass-containing fermentation solution in which the 2-keto-L-gulonic acid salt, e.g., the sodium, potassium, ammonium or calcium salt, is present in dissolved form. However, the free organic acids and their derivatives are the articles of commercial interest.
For example, in the industrial manufacture of D-ascorbic acid, the fermentatively produced 2-keto-L-gulonic acid must be transferred into an organic solvent, such as a lower alcohol. The salt form of 2-keto-L-gulonic acid, however, is practically insoluble in organic solvents. Therefore, for producing D-ascorbic acid with an industrial advantage, it is most preferable to employ the synthetic intermediate 2-keto-L-gulonic acid as a free acid.
Prior to conversion into ascorbic acid, however, 2-keto-L-gulonic acid must first be isolated from the fermentation broth. As described in U.S. Pat. No. 4,990,441, for example, 2-keto-L-gulonic acid can be recovered from a fermentation broth by a process comprising the steps of: (a) removing insoluble material from the broth by centrifugation in the presence of a flocculating agent, filtration in the presence of a flocculating agent and a filtration additive, or ultrafiltration; (b) removing inorganic cations by acidification; and (c) isolating 2-keto-L-gulonic acid by crystallization and drying. High yields of 2-keto-L-gulonic acid are difficult to obtain by this method, however, due to the number of steps required and the high solubility of 2-keto-L-gulonic acid in the crystallization mother liquor.
U.S. Pat. No. 5,852,211 describes a process for the conversion of the sodium salt of 2-keto-L-gulonic acid, which is present in an aqueous fermentation solution, into an alcoholic solution of the free acid. The disclosed process comprises the steps of: (a) crystallizing sodium 2-keto-L-gulonate monohydrate from an aqueous fermentation solution: (b) separating the sodium 2-keto-L-gulonate monohydrate crystals from the aqueous fermentation solution: (c) suspending the sodium 2-keto-L-gulonate monohydrate in a lower alcohol with acid at pH in a range from about 1.5 to about 3.5 whereby the acid is converted to the insoluble sodium salt of the acid and the sodium 2-keto-L-gulonate monohydrate is converted to free 2-keto-L-gulonic acid, and (d) removing the sodium salt of the acid to obtain an alcoholic solution of 2-keto-L-gulonic acid. Due to the number of steps and the high solubility of the sodium 2-keto-L-gulonic acid that remains in the crystallization mother liquor, however, high yields of 2-keto-L-gulonic acid are likewise difficult to achieve.
Known methods for the recovery and purification of other organic acids produced by fermentation, such as lactic or succinic acid, also contain numerous steps and/or produce less than optimal yields. See, e.g., U.S. Pat. Nos. 5,681,728; 5,522,995; 5,503,750; and 5,034,105. Accordingly, there remains a need for a simplified process for the concentration, recovery and purification of organic acids from aqueous solutions, such as fermentation broths, in high yields.